Sudden cardiac death (SCD) accounts for ~50% of all CHD deaths and, for the majority of victims, SCD is the first manifestation of heart disease. There is an accumulating body of evidence that fatty acids, particularly n-3 fatty acids, hold great promise as predictors of and preventive interventions against SCD, although studies have been inconsistent. These conflicting results may be due to differences in population characteristics (with and without CHD;men v. women) or methods of fatty acid assessment (dietary intake v. biomarker levels). Thus, more research is needed to understand the differences in risk among these various subgroups and to evaluate different methods of fatty acid measurements. Additionally, genetic and environmental influences on fatty acid metabolism are not well understood. Dr. Stephanie Chiuve's goals for this grant are to develop expertise in genetic epidemiology, advanced biostatistics, and dietary data collection, and then use this knowledge to study the role of fatty acids on SCD. Her career goal is to become an independent investigator in the field of "Nutritional Epidemiology of Cardiac Arrhythmic Disorders". Her primary mentor will be Dr. Christine Albert, a practicing clinical cardiac electrophysiologist and a leading epidemiologist in the field of cardiac arrhythmias and sudden cardiac death. In addition, several co-mentors with complimentary areas of expertise in biostatistics, genetic and cardiovascular epidemiology and fatty acid biology, who have strong records of successful mentorship, will supplement her training. During the K99 phase of this career development award, Dr. Chiuve will devote her time to scientific training in genetic epidemiology, biostatistics and fatty acid biology, through coursework, and mentored training through the analysis of dietary fatty acids and risk of SCD. She will also focus on her nonscientific career development by obtaining training in skills that will enhance the transition to independent investigator, including grant writing, scientific communication, mentoring and development and administration of a dietary questionnaire, and this training will continue throughout the award. During the R00 phase of the award, Dr. Chiuve use the skills gained in the K99 phase to study red blood cell (RBC) fatty acids and risk of SCD. She will also examine the influence of genetic variation in RBC fatty acids. She will investigate these aims within 6 large, NIH-funded prospective cohort studies that include both men and women and individuals with and without established CHD. Strengths of this proposal include the use of dietary and RBC fatty acid measures as means to predict individuals at high risk of SCD and the identification of subgroups that may benefit from a low-cost treatment such as modifying dietary fatty acid intake. These aims correspond to one goal in the NHLBI's strategic plan to "develop means to predict and prevent sudden cardiac death". PUBLIC HEALTH RELEVANCE: There are up to 400,000 sudden cardiac deaths (SCD) in the US annually, accounting for up to 20% of total mortality, and these deaths come with no forewarning. We aim to assess whether fatty acids, measured in the diet and in blood, can effectively predict risk of SCD and provide clinicians with the means to inform their patients of their heightened risk for SCD and suggest behavior or diet modification. This proposal is relevant to the NHLBI's strategic plan which aims "to develop non-invasive techniques, such as biological markers, to clinically identify patients at high risk of SCD".